The proposed epidemiologic study of a cohort of 137,223 adults who underwent multiphasic health checkups (MHC) at Kaiser Permanente Medical Care Program in San Francisco and Oakland, California, will examine the relationship of low blood total cholesterol (TC) to health outcomes. It is expected to confirm relations between TC and atherosclerotic causes of death (positive) and between TC and nonatherosclerotic causes of death (inverse) recently reported by a consortium of 19 cohort studies. It will be the first to study the relations of TC to many of the corresponding causes of morbidity. Several diseases are of specific interest because of observed inverse associations with TC:hemorrhagic stroke; lung, hematopoietic, lymphatic and liver cancers; traumatic death, including suicide; chronic obstructive pulmonary disease and other respiratory diseases; hepatitis, liver cirrhosis and other digestive diseases; demyelinating diseases; and infections. Those self-reporting pre-existing diseases at an MHC examination will be excluded from disease-specific analysis, and there is extensive self-report alcohol intake information for investigation. Because the database is so large, highly specific diseases and hypotheses can be studied. Using life table methods, the differential time course of hazard by TC category will be examined, to see whether hazard lessens as time passes. This study will ask whether there are diseases for which TC associations are weak for morbidity, but play a stronger role in terminal phases of life. Since many people have repeat multiphasic exams, it will shed light on the time course of TC during disease, and on which diseases result in a lowered TC early in their natural history. This research will study gender, age and cigarette smoking interactions, and will help to delineate the nature of the relationships of low TC with nonatherosclerotic diseases: the extent to which they are due to confounding by such factors as excessive alcohol intake and pre-existing morbidity, and the extent to which plausible biological mechanisms may be operating. The proposed study aiming to clarify observed associations is particularly relevant because of current public health policy directed at dietary modifications that reduce TC levels in the entire population. We need to know the likely effect of this program in those with low TC at the outset.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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Kaiser Foundation Research Institute
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Iribarren, Carlos; Jacobs, David R; Kiefe, Catarina I et al. (2005) Causes and demographic, medical, lifestyle and psychosocial predictors of premature mortality: the CARDIA study. Soc Sci Med 60:471-82
Iribarren, C; Markovitz, J H; Jacobs Jr, D R et al. (2004) Dietary intake of n-3, n-6 fatty acids and fish: relationship with hostility in young adults--the CARDIA study. Eur J Clin Nutr 58:24-31
Jacobs Jr, D R; Iribarren, C (2000) Invited commentary: low cholesterol and nonartherosclerotic disease risk: a persistently perplexing question. Am J Epidemiol 151:748-51
Iribarren, C; Jacobs Jr, D R; Sidney, S et al. (2000) Cigarette smoking, alcohol consumption, and risk of ARDS: a 15-year cohort study in a managed care setting. Chest 117:163-8
Iribarren, C; Sidney, S; Jacobs Jr, D R et al. (2000) Hospitalization for suicide attempt and completed suicide: epidemiological features in a managed care population. Soc Psychiatry Psychiatr Epidemiol 35:288-96
Iribarren, C; Jacobs Jr, D R; Sidney, S et al. (1998) Cohort study of serum total cholesterol and in-hospital incidence of infectious diseases. Epidemiol Infect 121:335-47
Claxton, A J; Jacobs Jr, D R; Iribarren, C et al. (1998) Association between serum total cholesterol and HIV infection in a high-risk cohort of young men. J Acquir Immune Defic Syndr Hum Retrovirol 17:51-7
Iribarren, C; Jacobs Jr, D R; Sidney, S et al. (1997) Serum total cholesterol and risk of hospitalization, and death from respiratory disease. Int J Epidemiol 26:1191-202
Iribarren, C; Jacobs, D R; Sadler, M et al. (1996) Low total serum cholesterol and intracerebral hemorrhagic stroke: is the association confined to elderly men? The Kaiser Permanente Medical Care Program. Stroke 27:1993-8
Jacobs Jr, D R; Muldoon, M F; Rastam, L (1995) Invited commentary: low blood cholesterol, nonillness mortality, and other nonatherosclerotic disease mortality: a search for causes and confounders. Am J Epidemiol 141:518-22